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Forskolin-induced Swelling in Intestinal Organoids: An In Vitro Assay for Assessing Drug Response in Cystic Fibrosis Patients
Published on: February 11, 2017
Enhanced glucose absorption in the jejunum of patients with cystic fibrosis
Abstract:
After oral D-xylose ingestion, cystic fibrosis patients have significantly higher blood levels of xylose than controls. The aim of this study was to examine whether nutrient absorption at the mucosal level is altered in cystic fibrosis. Steady-state perfusion experiments using isotonic test solutions were performed in 11 healthy controls and 10 cystic fibrosis patients. Net D-glucose absorption was higher in cystic fibrosis when the perfusate contained a glucose concentration of less than or equal to 50 mM. Kinetic analysis by three different methods, including Lineweaver-Burk analysis, revealed a lower apparent Km as well as a lower apparent Vmax in cystic fibrosis as compared with healthy controls (33.9 mM and 52.5 mmol/20 cm . h vs. 81.8 mM and 68.3 mmol/20 cm . h, respectively, p less than 0.01). Absorption of D-fructose and glycine demonstrated a tendency for increased net absorption in cystic fibrosis but the results were not significantly different. L-Xylose absorption and electrolyte movement were not altered in cystic fibrosis. Among several possible mechanisms investigated, a decrease in the apparent Km for glucose absorption would be consistent with a decrease in diffusion barriers overlying the jejunal mucosa in cystic fibrosis. Using an electrical method, the unstirred water layer thickness was significantly decreased in cystic fibrosis (546 +/- 41 micron in cystic fibrosis vs. 780 +/- 110 micron in controls, p less than 0.05). A decrease in the mucosal surface area in the cystic fibrosis group or an intrinsic defect in the mucosal glucose transport system could account for differences in the apparent Vmax values. We suggest, however, that enhanced absorption in cystic fibrosis is most likely due to a decrease in intestinal diffusion barriers possibly due to abnormal mucus overlying the intestinal mucosa.
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